한국인 당뇨병 및 비당뇨병 환자에서의 뇌혈관 질환 유무에 따른 PAI-1 촉진자 유전자형과 인슐린저항성에 관한 연구

오승준,김영설,박철영,김덕윤,김성운,양인명,김진우,최영길,팽정령,정경천 대한비만학회 2000 The Korean journal of obesity Vol.9 No.2

연구배경 : 혈전현상을 특징으로 하는 질환에서는 Plasminogen activator inhibitor-1 (PAI-1) 이 높은 활성도를 보이는데, PAI-1 치는 당뇨병, 심근경색증, 비만 등에서 높다고 밝혀진 바 있다. 또한 당뇨병 환자들의 합병증의 주요한 병인은 죽상경화증으로 혈전현상이 특징인 질환에서 증가하는 PAI-1이 당뇨병 환자에서 높다. 목적 : 정상인에서의 PAI-1 유전자 촉진자의 유전자형의 분포 및 혈액농도를 관찰하고, 당뇨병 및 뇌혈관 질환 환자군에서의 PAI-1 유전자 촉진자 유전자형의 분포 및 혈액농도를 측정하여 정상인과 차이점을 알아본다. 당뇨병 환자군에서의 혈장 PAI-1 치와 인슐린 저항성, 전구 인슐린 등과의 상관관계를 살펴보고, 인슐린저항성과 대혈관질환의 지표로 사용될 수 있는지 알아보았다. 방법 : 대상으로는 정상인 76명, 제2형 당뇨병 환자 56명, 뇌혈관질환이 동반된 제2형 당뇨병 환자 48명, 뇌혈관질환 환자 51명을 선택하여, 환자의 혈액에서 인슐린, 공복시 혈당, 전구인슐린, 중성지방, 총콜레스테롤 및 기타 생화학 검사 및 이학적 검사를 시행하였다. 환자의 DNA를 채취하여 전사개시 -675bp를 포함하는 대립형질 특이 시발체를 사용하여 중합효소 연쇄 반응을 실시하여, 그 유전자형을 판독하였다. 결과 : 정상 대조군 76명 (46.4±11.1세), 2형 당뇨병 환자 56명 (58.3±12.6세), 뇌경색증 환자 51명 (63.1±13.2세) 대상으로 하였다. PAI-1 촉진자 유전자형의 (4G/4G, 4G/5G, 5G/5G)빈도는 정상 대조군이 각각 23.7%, 75.0%, 1.3%, 뇌경색 환자군이 19.6%, 66.7%, 13.7%, 뇌경색이 동반된 당뇨병 환자군이 33.3%, 58.3%, 8.3% 였다. (X2=12.6, p=0.05). 이러한 사실은 서구인에 비해 4G/4G, 5G/5G 동형 유전자형이 낮은 결과였다. 각 군별 혈장 PAI-1 농도는 정상 대조군 13.4, 1.8 ~ 65.2 ng/mL (중앙값 , 범위 ) 2형 당뇨병 환자군 14.4, 2.9 ~ 47.8 ng/mL, 뇌경색 환자군 21.9, 6.2 ~ 154.7 ng/mL , 뇌경색이 동반된 2형 당뇨병 환자군 28.8, 3.2 ~ 139.3 ng/mL 로 차이를 보였다 (p=0.000). 전체 대상에서 PAI-1 촉진자 부위의 유전자형에 따른 PAI-1 활성도와 항원 농도는 차이를 보이지 않았다. 그러나 PAI-1 활성도는 혈중 중성지방, 전구인슐린, 체질량지수와 독립적인 상관관계를 보였다 (p=0.000, p=0.000 and p=0.005). 결론 : 결론적으로 PAI-1 촉진자 부위의 유전자형은 뇌경색증의 지표는 아니며, PAI-1 활성도를 결정짓는 인자는 유전적 요인보다는 혈중 중성지방, 전구 인슐린, 체질량지수와 같은 대사적 요인으로 생각된다. Plasminogen activator inhibitor-1 (PAI-1) is known be related to insulin resistance and several components of the large vascular disease. Notably, the high frequencies of diseases such as coronary heart disease or stroke are related to type 2 diabetes complications. We studied to find out whether the PAI-1 promother genotype could be a marker for cerebral infarction in type 2 patients. Subject patients were; 56 type 2 diabetics (age 58.3±12.6), 51 patients with cerebral infarction (age 63.1±13.2), 48 type 2 diabetics with cerebral infarction (age 64.8±9.3) , and 76 healthy control (age 46.4±11.1). The 4G/5G genotype of PAI-1 promoter was evaluated by polymerase chain reaction and endonuclease digestion. PAI-1 promoter genotype frequency (4G/4G, 4G/5G, 5G/5G) was 23.7%, 75.0% and 1.3% in healthy control, 17.9%, 67.9% and 14.3% in type 2 diabetes patients, 19.6%, 66.7% and 13.7% in cerebral infarction patients, 33.3%, 58.3% and 8.3% in type 2 diabetics with cerebral infarction (X^2=12.6, p=0.05). This finding is lower in frequency of 5G/5G homozygote than that reported in Caucasians. The plasma PAI-1 concentrations according to the disease were 13.4, 1.8 ~ 65.2 ng/mL (median, range) for healthy control, 14.4, 2.9 ~ 47.8 ng/mL for type 2 diabetes, 21.9 6.2 ~ 154.7 ng/mL for cerebral infarction , and 28.8, 3.2 ~ 139.3 ng/mL, for cerebral infarction with type 2 diabetes (p=0.000). In the all subjects, PAI-1 concentration and activity of PAI-1 promoter genotype did not show any significant difference. However, the PAI-1 activity was independently associated with serum triglyceride level, plasma proinsulin and BMI (p=0.000, p=0.000 and p=0.005 respectively). We concluded that PAI-1 genotype is not a marker for the cerebral infarction ; however, the genotype is related to PAI-1 concentration , and therefore it seems to be that metabolic factors such as triglyceride level or plasma proinsulin or BMI are more in relations with determining the PAI-1 concentration than the genotype.

간질환자의 간질 관련 외상

오동호,박운규,이영주,김희태,김승현,김주한,김명호,신동진 대한신경과학회 1998 대한신경과학회지 Vol.16 No.4

척수 경막외 혈관 기형에 의한 재발성 척수병증

오동호,김희태,박운규,이영주,김승현,김주한,김명호,박문향 대한신경과학회 1998 대한신경과학회지 Vol.16 No.5

제2형 당뇨병 남성 환자에서 유리 테스토스테론과 성호르몬 결합 글로블린 농도

남기덕,김영설,박철영,오승준,김덕윤,우정택,김성운,양인명,김진우,최영길 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.24 No.6

연구배경:인슐린저항성은 제2형 당뇨병과 심혈관질환의 주요한 위험 인자로 성호르몬과 상호 관계가 있다고 알려져 있다. 그러나 여성과는 달리 남성에서는 연령과 인슐린저항성에 따른 유리 테스토스테론과 성호르몬 결합 글로블린 농도의 변화에 대한 연구가 부족한 실정이다. 그러므로, 본 저자등은 제2형 당뇨병 남성 환자에서 정산인과 비교해서 유리 테스토스테론과 성호르몬 결합 글로블린 농도를 측정하고 연령에 따른 변화 정도를 알아보고자 하였다. 방법:대상 환자 모두에서 연령과 체질량지수, 총 콜레스테롤, 중성지방, 공복혈당과 인슐린 농도를 측정하였다. 혈중 유리 테스토스테론 농도는 방사면역측정법(radioimmunoassay)을 이용해서 측정하였고, 혈중 성호르몬 결합글로불린은 면역방사계측측정법(immunoradiometric assay)을 이용해서 측정하였다(Diagnostic System Laoratories, Wbster, TX, USA). 결과:1)제2형 당뇨병 남성 환자에서 정상 대조군 남성에 비해 성호르몬 결합글로불린은 104.1±35.0 vs 25.7±3.5 mole×10??로 의미 있게 높았으나(p<0.001), 유리 테스토스테론은 13.7±9.5 vs 13.6±6.5 ng/dL로 차이가 없었다. 2)연령과 성호르몬 결합 글로블린 사이의 상관 계수는 제2형 당뇨병 남성 환자에서 0.40로 중등고의 양의 상관 관계를 보였고(p<0.001), 정상 대조군 남성에서 0.11로 유의한 상관 관계를 보이지 않았다. 연령과 유리 테스토스테론 사이의 상관 계수는 제2형 당뇨병 남성 환자에서 0.08, 정상 대조군 남성에서-0.17로 모두에서 유의한 상관 관계를 보이지 않았다. 3)연령과 체질량지수를 보정한 후에 제2형 당뇨병 남성 환자와 정상 대조군 남성에서 혈중 인슐린 농도, 유리 테스토스테론과 성호르몬 결합 글로블린 사이에는 상관 관계가 없었다. 결론:제2형 당뇨병 남성 환자에서 정상 남성에 비해 성호르몬 결합 글로블린 농도가 증가되어 있었으며, 유리 테스토스테론은 차이가 없었다. 연령이 증가함에 따라 성호르몬 결합 글로블린이 제2형 당뇨병 남성 환자에서 정상 남성에 비해 증가 폭이 의미있게 컸으며, 유리 테스토스테론은 변화가 없었다. Background: Insulin resistance is a risk factor for cardiovascular disease and type 2 diabetes mellitus. There are many previous studies indicating that insulin lowers serum sex hormone-binding globulin levels, and there is inverse correlation between insulin resistance and serum sex hormone-binding globulin levels in women. However, in men, a limited number of studies are available to explain the effect of sex hormone on age and insulin. Therefore, the present study was undertaken to investigate the relationship among free testosterone, hormone-binding globulin and age in type 2 diabetic men and control subjects. Method: Age, body mass index, total cholesterol, triglyceride, fasting blood sugar, and insulin concentrations were examined on 89 type 2 diabetic men and 47 control subjects. The free testosterone level was measured by commercially available double-antibody system (Radioimmunoassay). The sex hormone-binding globulin level was also measured by commercially available double-antibody system(Immunoradiometric assay). Results: 1) Sex hormone-binding globulin level was significantly increased in patients with type 2 diabetes. However, there was no significantly difference in free testosterone level between the two groups. 2) Sex hormone-binding globulin was positively correlated with age (r=0.4, p <0.001) in patients with type 2 diabetes. Sex hormone-binding globulin and free testosterone were not correlated with age in control sujects. 3) Free testosterone and sex hormone-binding globulin concentrations were not significantly related to serum insulin concentration after adjusting for age and body mass index. Conclusions: We observed increased sex hormone-binding globulin concentration in diabetes man, and was a positively related to age. Further studies are needed to understand the relationships between age, insulin resistance, testosterone, and sex hormone-binding globulin concentrations(J Kor Diabetes Asso 24:699~707,2000).

포도당과 이소프로테레놀에 의한 시상하부의 소마토스타틴 분비가 갑상선자극호르몬방출호르몬에 의한 갑상선자극호르몬에 미치는 효과

박철영,양인명,오승준,김덕윤,우정택,김성운,김진우,김영설,최영길 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.4·5

Impact of Interferon-Based Treatment on Quality of Life and Work Related Productivity from the Korean Cohort in the MOSAIC Study

( Sang Hoon Ahn ),( Won Hyeok Choe ),( Yoon Jun Kim ),( Jeong Heo ),( Dorota Latarska-smuga ),( Jiho Kang ),( Seung Woon Paik ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Chronic Hepatitis C Virus (HCV) infection increases the risk for progressive liver disease, hepatocellular carcinoma and negatively impacts the patient’s quality of life. HCV treatment is evolving with direct acting antivirals but IFN based therapy has been the standard of care for many years and remains available in some countries. The MOSAIC study aims to characterize patients with chronic HCV infection and assess the impact of IFN-containing treatment on health-related quality of life, work related productivity and health care utilization. Methods: MOSAIC is an international prospective multicenter observational study that has been conducted in 20 countries. Consecutive patients with chronic HCV infection were enrolled and those who initiated an IFN based regimen were prospectively followed for 48 weeks. We report results from the Korean cohort Results: 100 patients were enrolled: 86 were treatment naïve and 14 were treatment experienced. 33 patients initiated an IFN based regimen: 6 patients started IFN + RBV, 26 patients started Peg-IFN + RBV, none started Peg-IFN + RBV + DAA and 1 patient received other treatment. Among the treated cohort, demographic and disease characteristics were the following: the mean age was 54.5 years; 14 patients were male. 14 had minimal or no fibrosis, 2 portal fibrosis, 3 bridging fibrosis and 6 patients suffered from cirrhosis. HCV Genotype distribution was as follows: genotype 1: 11; genotype 2: 19 and genotype 3: 3. Table 1 describes the results at baseline and changes over 4, 12 and 48 weeks and end-of-treatment (EOT) for the quality of life and work productivity outcome measures (EQ-5D-5L, HCV-PRO and WPAI). Conclusions: Results from the Korean cohort of the MOSAIC study show a moderate trend for deterioration of health-related quality of life and work productivity associated with IFN based treatment for patients with chronic HCV infection during treatment period. Acknowledgements: The design, study conduct, analysis, and financial support of MOSAIC study were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the content of the abstract. All authors had access to all relevant data and participated in writing, review, and approval of this abstract. Medical writing support was provided by Olivier Van de Steen of Medeor-consulting, funded by AbbVie. Disclosures: Sang Hoon Ahn: served as an advisor and lecturer for Bristol-Myers Squibb, Gilead Sciences, F.Hoffmann-La Roche, Merck, AbbVie, and has received unrestricted grants from Bristol-Myers Squibb, Gilead Sciences, and F. Hoffmann-La Roche for investigator- initiated trials Won Hyeok Choe: Nothing to disclosure Yoon Jun Kim: Nothing to disclosure Jeong Heo: received a grant from GSK; Research support from BMS, and Roche; Advisor for Abbvie, BMS, Gilead Sciences, Pharma Essentia, SillaJen, and Johnson & Johnson. Dorota Latarska-Smuga, Jiho Kang: are employees of AbbVie, Inc. and may hold stock or stock options. Seung Woon Paik: received grant and research support from AbbVie, BMS, Gilead, GSK, Merck, Novartis, and Roche

Protective effect of Korean Red Ginseng against FK506-induced damage in LLC-PK1 cells

Dahae Lee,Ki Sung Kang,Jae Sik Yu,Jung-Yoon Woo,Gwi Seo Hwang,Dae-Woon Eom,Seung-Hoon Baek,Hye Lim Lee,Ki Hyun Kim,Noriko Yamabe 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.3

Background: Compound FK506 is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In this study, the protective effect of Korean Red Ginseng (KRG) against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated. Methods: LLC-PK1 cells were exposed to FK506 with KRG and cell viability was measured. Western blotting and RT-PCR analyses evaluated protein expression of MAPKs, caspase-3, and KIM-1. TLR-4 gene expression was assessed. Caspase-3 activities were also determined. The number of apoptotic cells was measured using an image-based cytometric assay. Results: The reduction in LLC-PK1 cell viability by 60mM FK506 was recovered by KRG cotreatment in a dose-dependent manner. The phosphorylation of p38, p44/42 MAPKs (ERK), KIM-1, cleaved caspase-3, and TLR-4 mRNA expression was increased markedly in LLC-PK1 cells treated with 60mM FK506. However, with the exception of p-ERK, elevated levels of p-p38, KIM-1, cleaved caspase-3, and TLR-4 mRNA expression were significantly decreased after cotreatment with KRG. Activity level of caspase-3 was also attenuated by KRG cotreatment. Moreover, image-based cytometric assay showed that apoptotic cell death was increased by 60mM FK506 treatment, whereas it was decreased after cotreatment with KRG. Conclusion: Taken together, these results suggest that the molecular mechanism of KRG in the FK506-induced nephrotoxicity may lead to the development of an adjuvant for the inhibition of adverse effect FK506 in the kidney.

강변여과에서 파일럿규모 수평집수관의 수두분포 연구

정재민(Jae Min Jeong),박재영(Jae Young Park),이종진(Jong Jin Lee),김용운(Yong Woon Kim),김승현(Seung Hyun Kim) 大韓環境工學會 2013 대한환경공학회지 Vol.35 No.5

강변여과용 수평집수관을 모사하는 파일럿 규모의 모래통 실험을 수행하였으며, 다양한 출구유속에 대한 수평집수관에서의 수두분포를 구하였다. Kim24)이 수행한 실험실 규모의 수평집수관에서의 손실수두에 Kim25)이 개발한 이론 즉, 작은 규모의 수평집수관에서의 손실수두로부터 큰 집수관의 손실수두를 계산하는 방법을 적용하여 본 연구의 관측치와 비교함으로써 Kim25)의 이론이 타당함을 알 수 있었다. 또한, 이들의 이론을 적용하여 본 연구에서의 관측치로부터 실규모 집수관에서의 수두분포를 구하는 방안을 예를 들어 설명함으로써 강변여과의 수평집수관 설계방법을 제시하였다. A pilot-scale sand-box experiment simulating a lateral of collector well used in riverbank filtration was performed, and hydraulic head distributions along the lateral were measured according to the various drawdowns at the well. The results of this experiment were compared to the predicted values obtained using a theory previously developed by Kim25) in order for its validation. This theory predicts the head loss in a large-scale lateral given the loss in a small-scale one, and to have actual values for comparison, the results from a lab-scale experiment previously performed by Kim24) were employed. Comparing the experimental values to the extrapolated value indeed confirmed the validity of the theory. A procedure to determine the hydraulic head distribution of a practical-scale lateral was also presented applying the theory to the experimental result of this study in an effort to show the process of lateral design for riverbank filtration.

Protective effect of Korean Red Ginseng against FK506-induced damage in LLC-PK1 cells

Lee, Dahae,Kang, Ki Sung,Yu, Jae Sik,Woo, Jung-Yoon,Hwang, Gwi Seo,Eom, Dae-Woon,Baek, Seung-Hoon,Lee, Hye Lim,Kim, Ki Hyun,Yamabe, Noriko The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.3

Background: Compound FK506 is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In this study, the protective effect of Korean Red Ginseng (KRG) against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated. Methods: LLC-PK1 cells were exposed to FK506 with KRG and cell viability was measured. Western blotting and RT-PCR analyses evaluated protein expression of MAPKs, caspase-3, and KIM-1. TLR-4 gene expression was assessed. Caspase-3 activities were also determined. The number of apoptotic cells was measured using an image-based cytometric assay. Results: The reduction in LLC-PK1 cell viability by $60{\mu}M$ FK506 was recovered by KRG cotreatment in a dose-dependent manner. The phosphorylation of p38, p44/42 MAPKs (ERK), KIM-1, cleaved caspase-3, and TLR-4 mRNA expression was increased markedly in LLC-PK1 cells treated with $60{\mu}M$ FK506. However, with the exception of p-ERK, elevated levels of p-p38, KIM-1, cleaved caspase-3, and TLR-4 mRNA expression were significantly decreased after cotreatment with KRG. Activity level of caspase-3 was also attenuated by KRG cotreatment. Moreover, image-based cytometric assay showed that apoptotic cell death was increased by $60{\mu}M$ FK506 treatment, whereas it was decreased after cotreatment with KRG. Conclusion: Taken together, these results suggest that the molecular mechanism of KRG in the FK506-induced nephrotoxicity may lead to the development of an adjuvant for the inhibition of adverse effect FK506 in the kidney.

Propofol 정맥 주사 시 Metoclopramide의 통증 완화 효과

김수진,박은지,안승원,김웅,김미운,임현술 대한마취과학회 2002 Korean Journal of Anesthesiology Vol.43 No.5

Background: Propofol is a good induction agent. but it has a disadvantage of pain on intravenous injection. Pretreatment of metoclopramide or lidocaine have been reported to reduce pain on injection. thus, we have evaluated the quantity and quality of anagesic effect of metoclopramide and lidocaine. We observed differences in quality of pain according to venous cannula sizes and intravenous injection sites as well as nausea and vomiting in the postoperative state. Methods: Eighty patients scheduled for an elective operation by general anesthesia were chosen according to ASA (Ⅰ or Ⅱ) and divided into four groups randomly. Each group was injected through venous cannulas with normal saline (control group), metoclopramide 5 mg (group 1), netoclopramide 10 mg (group 2), or 2% lidocaine 40 mg (group 3) respectively. Then, propofol was injected of a 2 mg/kg dose with 0.5 ml/sex to all groups and we asked questions about injection pain after 10 seconds. Results: Pain relief was shown in all groups compared with the control. but metoclopramide 10 mg and lidocaine 40 mg pretreatment groups showed significant pain reief. Pain was relieved significantly when the drug was injected in the antecubital area. Postoperative nausea and vomiting were not observed. Conclusions: Metoclopramide 10 mg or lidocaine 40 mg pretreatment to induction by propofol revealed a good analgesic effect for propofol injection pain. (Korean J Anesthesiol 2002; 43: 558~565)